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Biomedical subjects

A Hashimoto

Publications and source records attributed to A Hashimoto.

At least 109 records · Page 6Linked to original sources

Linoleic acid and alpha-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin.

This study was conducted to evaluate the effects of unsaturated fatty acids on ultraviolet-induced hyperpigmentation of the skin. An efficient lightening effect was observed following topical application of linoleic acid or alpha-linolenic acid to UV-stimulated hyperpigmented dorsal skin of brownish guinea pigs. The number of melanocytes in the treated skin was similar to the number in the skin of the pigmented control, indicating that the pigment-lightening effect was not due to depletion of melanocytes. In vitro experiments using cultured murine melanoma cells showed that melanin production was inhibited most effectively by alpha-linolenic acid, followed by linoleic acid and then by oleic acid. Furthermore, the turnover of the stratum corneum, which plays an important role in the removal of melanin pigment from the epidermis, was accelerated by linoleic acid and by alpha-linolenic acid. Taken together, the results suggest that the pigment-lightening effects of linoleic acid and alpha-linolenic acid are, at least in part, due to suppression of melanin production by active melanocytes, and to enhanced desquamation of melanin pigment from the epidermis.

Administration, Topical↗

TAC-101, a benzoic acid derivative, inhibits liver metastasis of human gastrointestinal cancer and prolongs the life-span.

We examined the anti-tumor effect of a novel benzoic acid derivative, TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid) on models with liver metastasis. Oral administration of TAC-101 significantly inhibited spontaneous liver metastasis of AZ-521 (human gastric cancer ) by orthotopic implantation to athymic nude mice. It also inhibited both the liver metastasis of AZ-521 induced by intrasplenic injection and the secondary lung metastasis from the liver. In addition, TAC-101 inhibited the proliferation of Co-3 (human colon adenocarcinoma) that formed a single nodule in the liver of athymic nude mice by intrahepatic implantation. The growth inhibitory effect of TAC-101 on AZ-521 experimental liver metastasis was observed when treatment was started on day 7, 14, or 21 which may correspond to the progressive stage of liver metastasis in clinical settings. Multiple administration of TAC-101 (8 mg/kg/day) significantly prolonged survival time of the animals with liver metastasis by intrasplenic injection of AZ-521 (T/C = 230%) and A549 (human lung adenocarcinoma; T/C = 186%). These effects of TAC-101 were stronger than those of 5-FU, CDDP or ATRA. Furthermore, TAC-101 inhibited the binding of AP-1 to DNA on electrophoretic mobility shift assay using nuclear extract of AZ-521 cells, although ATRA did not inhibit. These findings suggested that TAC-101 may be a candidate for a new class of anti-cancer agents for liver metastasis.

Adenocarcinoma↗

4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) inhibits the intrahepatic spread of hepatocellular carcinoma and prolongs the life-span of tumor-bearing animals.

We examined the in vivo anti-tumor activity of the benzoic acid derivative, TAC-101 (4-[3,5-bis(trimethylsilyl)benzamido] benzoic acid), for intrahepatic spread of JHH-7 human hepatocellular carcinoma (HCC) cells and its mechanism of action. Oral administration of TAC-101 markedly inhibited liver tumor of JHH-7 cells and prolonged the life-span of tumor-bearing mice without affecting the body weight. The life-prolonging effect of TAC-101 was more effective than that of other anti-cancer agents including CDDP, 5-FU, and CPT-11 (T/C (%) of life-span; 181 to 219, 128, 133, and 142%, respectively). In vitro, TAC-101 at the concentration of more than 10 microM showed direct cytotoxicity against JHH-7 cells caused by induction of apoptosis. Hepatocyte growth factor (HGF) enhanced the invasive ability of JHH-7 cells without affecting the cell viability. Non-cytotoxic concentrations of TAC-101 inhibited the JHH-7 invasion induced by HGF and down-regulated the expression of c-MET protein in a concentration-dependent manner. In summary, these results suggest that TAC-101 would be useful for a new class of therapeutic agents and that it may improve the prognosis of patients with liver-tumors including metastasizing tumor and HCC.

Animals↗

Ultrasonographic and serologic studies of experimental cysticercosis in rats infected with Taenia taeniaeformis.

Rats experimentally infected with Taenia taeniaeformis were followed-up until 14 weeks post inoculation with eggs (PIE) by hepatic ultrasonographic (US) image and serum antibody response analyses. Parasitic cysts could be imaged as small (2 mm in diameter) anechoic areas with or without a parenthesis-like echogenic small line from two weeks PIE. Immunoblot analysis using antigens from oncospheres (TtO), 30-day-old (TtM-30) and 300-day-old metacestodes (TtM-300) revealed that: (1) these three different developmental stages showed their own unique patterns suggesting the presence of stage-specific antigens; (2) faint IgM antibody responses to some components of TtO and TtM-30 or TtM-300 could be detected from one and two weeks PIE, respectively, and (3) IgG responses to some major components of both TtO and TtM-300, and TtM-30 were easily detected from four and five weeks PIE onwards, respectively. Both TtO and TtM (especially TtM-300) appeared to be highly useful for detection of antibody responses in experimentally infected rats. Due to the easiness in preparation of antigens, fully developed metacestodes may be the best candidate antigens for serodiagnosis. These results strongly suggest that both US image and antibody analyses using antigens from fully developed metacestodes are useful for detection of the early stage of cysticercosis in laboratory animal model.

Animals↗

Comparison of attenuation and liver-kidney contrast of liver ultrasonographs with histology and biochemistry in dogs with experimentally induced steroid hepatopathy.

Digital analysis of liver ultrasound images (USGs) was compared to histological and serum enzyme activity results in dogs with steroid-induced hepatopathy. Steroid hepatopathy was used as a model for diffuse liver diseases. Prednisolone administration resulted in increased acoustic backscatter (hyperechogenicity) of the liver with reference to the kidney and significant depth attenuation (hyper-attenuation). Absolute changes were determined by histogram analysis of echo means (Ems) of area samples (1 x 1 cm) of liver and kidney at the depth of 2 cm (liver-kidney contrast) and at 2 cms and 4 cm (depth attenuation). Liver-kidney contrast histograms correlated well with histology but were more sensitive than serum enzyme activity and subjective visual interpretation. Depth attenuation was the earliest detectable acoustic change. These results suggested that depth attenuation is an early and sensitive indicator of steroid hepatopathy. Liver-kidney contrast correlates well with histology and may complement biopsy examination during follow-up studies.

Alanine Transaminase↗

Endoscopic and transcutaneous ultrasonographic findings and grey-scale histogram analysis in dogs with caerulein-induced pancreatitis.

Endoscopic ultrasonography (EUS), grey-scale histogram analysis of EUS images, and transcutaneous ultrasonography (TUS) were done in four dogs with caerulein-induced pancreatitis. One other dog was subjected to laparotomy and biopsy specimens were collected for histopathology. By EUS, the pancreatic lesions were first detected at 60 minutes after the start of caerulein infusion. They were detected after 120 to 150 minutes when using TUS. EUS findings included swelling, a more distinct lobular pattern, subcapsular hypoechoic areas, and anechoic stripes through the pancreatic tissue. No marked changes in the histogram analysis was seen until 30 minutes. From 30 to 60 minutes, a decrease in the mean brightness of the pancreatic tissue was observed. These changes in mean brightness reflected histopathological findings showing vacuolization of acinar cells and interstitial oedema of the pancreas. These findings indicated that EUS can detect slight and diffuse changes in pancreatic tissue. Furthermore, grey-scale histogram analysis detects histopathological changes more sensitively than endoscopic ultrasound images.

Animals↗

Reduction of caveolin-1 expression in tumorigenic human cell hybrids.

Studies on human cell hybrids of a cervical carcinoma cell line, HeLa, and normal fibroblasts have indicated that the tumorigenicity of these cells is under the control of a putative tumor suppressor on chromosome 11, although the nature of this suppressor remains unknown. We examined the expression of caveolin-1, a protein component of caveolae of the plasma membrane in these cell hybrids. The non-tumorigenic cell hybrid, CGL1, and normal fibroblast WI38 cells expressed 21-24 kDa caveolin-1, whereas in tumorigenic hybrid CGL4 as well as in the parental HeLa cells, the level of caveolin-1 was markedly reduced. Caveolin-1 expression was also reduced in gamma-ray-induced tumorigenic clones (GIMs) isolated from CGL1 cells, whereas non-tumorigenic irradiated cells expressed the same level of caveolin-1 as CGL1 cells. In accordance with these changes, the cellular level of caveolin-1 mRNA was reduced in the tumorigenic CGL4 cells and GIMs without any detectable changes in the caveolin-1 gene. However, the in vivo tumor growth of CGL4 cells was not altered when caveolin-1 was stably overexpressed through the transfection of a human caveolin-1 cDNA. These results suggest that reduction of caveolin-1 expression is necessary but not sufficient for emergence of the tumorigenic phenotypes of HeLa cell hybrids. Possible roles of the putative tumor suppressor in the control of gene expression are also discussed.

Blotting, Northern↗

[Clinical study on mechanism of Pneumocystis carinii pneumonia by polymerase chain reaction].

Pneumocystis carinii is a human respiratory pathogen which causes fatal pneumonia in patients under immunosuppressed or immune deficient conditions. Recent work have documented the usefulness of the polymerase chain reaction (PCR) method in the detection of P. carinii from clinical samples. Therefore, we described our experience in using PCR method in the detection of P. carinii from respiratory samples. In our study, bronchial washing or BALF were good for diagnosis of P. carinii pneumonia (PCP) by PCR. However, PCR method in the detection of P. carinii from swab or sputum was too sensitive because small numbers of P. carinii organisms might be insignificant in causing the disease. It might reveal colonization or asymptomatic carrier state in the upper respiratory tract. Therefore, our result suggested that colonization or asymptomatic carrier state in the upper respiratory tract could eventually evolve into PCP. This would also facilitate basic progress in the pathology or epidemiology of P. carinii infection. In addition, an usefulness of prophylactic therapy for PCP was documented by PCR.

Bronchoalveolar Lavage Fluid↗

Evaluation of PCR for detection of DNA specific for Aspergillus species in sera of patients with various forms of pulmonary aspergillosis.

Pulmonary aspergillosis is classified into invasive, saprophytic, and allergic forms. In this study, we evaluated the usefulness of PCR for differentiating between different forms of aspergillosis or in monitoring disease activity during treatment by detecting DNA specific for Aspergillus species in the serum. Nested PCR was used to detect Aspergillus DNA in the sera of 30 patients with various forms of pulmonary aspergillosis. The results were compared with those of latex agglutination tests for detecting galactomannan antigen. We also examined the serial changes in the results of nested PCR during and after treatment of a subgroup of patients with invasive pulmonary aspergillosis with amphotericin B. The highest proportion of positive nested PCR results were in patients with invasive aspergillosis (10 of 12; 83%), while patients with pulmonary aspergilloma had the lowest frequency of positive tests (1 of 9; 11%). These results suggested that the sensitivity of the nested PCR depends on the extent of invasion by Aspergillus species. Serial assays showed that the results of nested PCR became negative shortly after commencement of antifungal treatment and that such changes did not correlate with clinical responsiveness to treatment. Our results indicate the potential usefulness of nested PCR with serum samples for the diagnosis of invasive aspergillosis and the detection of a shift in the status of infection from a noninvasive type to invasive aspergillosis. However, the results of the nested PCR did not correlate with the response to antifungal treatment.

Adult↗

Preparation and characterization of everted membrane vesicles from cells of Staphylococcus aureus.

We developed a method for the preparation of everted membrane vesicles from cells of Staphylococcus aureus. The cells were first treated with ampicillin to weaken the peptidoglycan layer, then the cells were passed through a French press cell. The resulting vesicles were roughly 0.1 microm in diameter, judging from electron microscopic observations. We detected fairly high membrane-bound ATPase activity in the membrane vesicles. We observed respiratory-driven quenching of quinacrine fluorescence, which indicates that inward H+ transport took place. These results indicate that the vesicles are everted. We characterized the membrane-bound ATPase. We also detected Na+/H+ antiport, erythromycin/H+ antiport and chloramphenicol/H+ antiport activities in the membranes of S. aureus.

Adenosine Triphosphatases↗

[Study on the "signal" constituents for the evaluation of animal crude drugs. V. The "signal" constituents for the identification of Lumbricus in cold medicines].

Lumbricus has been widely used as an antifebrile agent in cold medicines. The identification of each agent, especially crude drugs in formulations, is very important from the viewpoint of quality control. In this paper, the contents of amino acids, organic acids, nucleic acid components and cholesterol were investigated to evaluate the "signal" constituents of Lumbricus and Lumbricus extracts in the medicines. It was found that the content pattern of these components of Lumbricus extracts was almost the same as those in Lumbricus itself. However, most of other crude drugs used in cold medicines, also contain some of these components. It was difficult to identify Lumbricus through the difference in the content pattern of these components. Therefore, we focused on such five constituents as cholesterol, lombricine, lactic acid, inosine and hypoxanthine, because lombricine is a characteristic amino acid of Lumbricus and the contents of other four components in Lumbricus are relatively high compared with those of other crude drugs. Lombricine and inosine were detected clearly in all seven commercial formulations investigated, and cholesterol and hypoxanthine were also detected except two commercial formulations. However, the detection of lactic acid was not successful in all formulations, because of the presence of interfering components. In the seven commercial cold medicines, lombricine and inosine were found to be useful as "signal" constituents for the identification of Lumbricus in cold medicines.

Analgesics, Non-Narcotic↗

[Evaluation of new method for diagnosis of opportunistic fungal infection].

New methods for the possible presence DNA specific for Aspergillus or Trichosporon species were developed. In aspergillus PCR, Aspergillus l8S rRNA encoding gene was amplified from five strains of Aspergillus species by the nested PCR but not from other microorganisms. Results of preliminary investigation of this method demonstrated efficient detections of Aspergillus species in serum samples of rats model of aspergillosis and 29 patients with invasive aspergillosis. In trichosporon PCR, Trichosporon 26S rRNA encoding gene was amplified from two strains of Trichosporon species, and detected by the nested PCR in 64 % of serum samples of patients with trichosporonosis, while glucuronoxylomannan antigen was detected in 55 % of samples. The high sensitivity and specificity of the nested PCR indicate that the assay can provide early diagnosis with sufficient accuracy to be clinically useful for patients with opportunistic fungal infection.

Adult↗

Saccharides as osmotic agents in peritoneal dialysate: determination of molecular weight essential for more efficient fluid removal.

Glucose has widely been used as an osmotic agent in continuous ambulatory peritoneal dialysis (CAPD) but owing to its low molecular weight (MW), ultrafiltration (UF) in a 6-hour dialysate exchange does not appear sufficient. Thus, in the present study, a search was made to find saccharides that would ensure optimal UF, exceeding that obtained with glucose in a 6-hour dwell period. Rats were intraperitoneally infused with peritoneal dialysate (20 mL/body) containing the same molar concentrations (75.5 mM, 126 mM, or 204 mM) of various osmotic agents including glucose (monosaccharide, MW = 180.16) at concentrations of 1.36%, 2.27%, and 3.86%; maltose (disaccharide, MW = 342.30) at concentrations of 2.58% and 4.32%; maltotriose (trisaccharide, MW = 504.44), at concentrations of 3.81% and 6.36%; and maltopentaose (pentasaccharide, MW = 828.72) at concentrations of 6.26% and 10.4%. Intraperitoneal-fluid volume was measured at 1, 2, 3, 4, and 6 hours. With glucose as the osmotic agent, maximal UF was noted at 2 to 4 hours. UF was more efficient at 6 hours with maltotriose or maltopentaose as the osmotic agent. Even with a trisaccharide or pentasaccharide (molecular weights of 500 to 830), UF at 6 hours was found more efficient, as evidenced by the delay in peritoneal absorption. Fluid removal in 6 hours should be greater when using a dialysate containing oligosaccharides such as maltotriose or maltopentaose in place of glucose.

Animals↗

In vitro and in vivo generation and kinetics of glycosylation products in peritoneal dialysis effluents.

There are indications that advanced glycosylation end-products (AGEs) may affect in some manner the functions of the peritoneum. Only a few reports discuss the actual generation of glycosylated proteins and the intraperitoneal kinetics involved during continuous ambulatory peritoneal dialysis (CAPD). To demonstrate the formation of AGEs and their time-courses in peritoneal dialysis (PD) effluents, measurements were made of furosine, carboxymethyl lysine (CML), and pentosidine as glycosylation markers in vitro and in vivo using PD effluents obtained every 2 hours for up to 8 hours from 3 nondiabetic CAPD patients. Furosine and CML were found to be generated relatively early (within 6 hours), and their de novo formation was markedly enhanced subsequent to glucose addition. Furosine and CML production increased in proportion to glucose concentration. Pentosidine production did not change with time for up to 24 hours, and was not induced by glucose during this period. Carboxymethyl lysine production appeared to be suppressed in vitro with the addition of serum protein. Furosine in the intraperitoneal dialysate was initially the same as that in the plasma, but increased to twice as much in just 2 hours in vivo. Production of CML increased, but apparently was suppressed with leakage of plasma protein into the dialysate; this possibly may have been due to dilutional or antiglycation effects in the plasma. No stimulation of pentosidine production could be detected in the intraperitoneal dialysate even at 8 hours. The initiation of glycosylation of peritoneal proteins, with generation of furosine and CML but not pentosidine, is clearly shown by the present results to occur relatively early in the intraperitoneal dialysate, i.e., within a matter of hours.

Adult↗

Effect of hyperbaric oxygen on intercellular adhesion molecule-1 (ICAM-1) expression in murine lung.

BACKGROUND: The lung is one of the most susceptible organs to the toxic effect of high pressure oxygen. However, the contribution of the cellular adhesion molecules and inflammatory leukocytes in the pulmonary oxygen toxicity, especially in an acute exudative phase, is not well understood. In the present study we have investigated the toxic effect of hyperbaric oxygen (HBO) expressed by the analysis of the intercellular adhesion molecule-1 (ICAM-1) on the pulmonary vascular endothelial cells and leukocyte function. METHODS: Mice were exposed to HBO at 3 ATA of PO2 for 3, 4, or 6 h. Expression of ICAM-1 was serially observed by immunohistochemical analysis. The oxidative metabolic activity of the leukocytes was measured after HBO exposure. RESULTS: After HBO exposure an increase in the number of pulmonary interstitial leukocytes (PIL) and bronchoalveolar lavage (BAL) was observed at 72 h and 48 h, respectively. The expression of ICAM-1 was strongly enhanced immediately after HBO exposure and this enhancement lasted for 24 h. This suggests the importance of enhanced expression of adhesion molecules in the generation of pulmonary oxygen toxicity. However, we could not detect increased chemiluminescence activity in the early phase in the BAL cells and PIL. CONCLUSION: Expression of ICAM-1 was enhanced from the very early stage after HBO, but neither accumulation of leukocytes in the lung nor increase in the chemiluminescence activity were observed in this phase. Therefore, activation of inflammatory leukocytes in the pulmonary oxygen toxicity may occur only after prolonged (more than 4 h) or repetitive exposures to HBO.

Animals↗

[Antitumor activity of miproxifene phosphate (TAT-59) against human mammary carcinoma].

DP-TAT-59, an active metabolite of miproxifene phosphate (TAT-59), showed a strong anti-proliferating activity against ER-positive human mammary carcinoma cell lines, MCF-7 and T-47D, in the presence of 1 nM of estradiol. The ED50 value of DP-TAT-59 for each cell line was 30-fold lower than that of tamoxifen. TAT-59 suppressed the growth of mammary carcinoma, MCF-7 and Br-10, xenografted into nude mouse at a dose of 5 mg/kg/day, which is equivalent to 20 mg/body of daily dose to the patients. TAT-59 inhibited the growth of tamoxifen-resistant breast cancer cell lines, R-27 and FST-1, but not tamoxifen, suggesting the possible efficacy of TAT-59 for tamoxifen-refractory patients. DP-TAT-59 and DM-DP-TAT-59, major metabolites of TAT-59 detected in blood after oral administration in the patients, exhibited equal growth-inhibitory activity against human mammary tumor xenograft, meaning the antitumor activity of TAT-59 may equally depend on these two metabolites. In uterotrophic testing using both immature mice and ovariectomized rats, while the effective dose of TAT-59 was lower than that of tamoxifen, TAT-59 showed dose-dependent estrogenic activity against their uteri, similar to tamoxifen. These results suggested that TAT-59 had a stronger antagonistic activity against estrogen-dependent mammary tumor than tamoxifen. We expect that TAT-59 will become an effective therapeutic agent for patients with high estrogen levels in their blood, such as premenopausal women, and the patients with whom the tamoxifen modality failed.

Animals↗

The canine alkaline phosphatases: a review of the isoenzymes in serum, analytical methods and their diagnostic application.

This paper reviews the alkaline phosphatases in canine serum, the analytical methods used for qualitative and/or quantitative detection of these isoenzymes, and the diagnostic significancy of each of these isoenzymes. The paper further describes some of the latest advances in our knowledge of the canine alkaline phosphatases and possible areas of future research.

Alkaline Phosphatase↗

Outcome significance of thallium-201 and iodine-123-BMIPP perfusion-metabolism mismatch in preinfarction angina.

UNLABELLED: The relevance of brief antecedent ischemia to preservation of myocyte viability and cardiac function is still controversial in humans. Dysfunctioning but viable myocardium shows impaired fatty acid metabolism despite restored coronary perfusion. We asked whether preinfarction angina might be related to preservation of cell viability and better functional recovery in comparison with impaired fatty acid metabolism. METHODS: Tomographic imagings with thallium and beta-methyl-p-iodophenyl penta-decanoic acid (BMIPP) were performed in 32 patients with first acute myocardial infarction who received primary coronary angioplasty: 20 patients with preexisting angina before infarction (Group A) and 12 without (Group B). Thallium and BMIPP abnormalities were quantified as a severity index by a polar map. Regional function was quantified by ventriculography and followed up. RESULTS: Despite no significant difference in coronary risk factors, cardiac function and angiographic findings, the thallium severity index was significantly lower than that of BMIPP (62+/-45 versus 96+/-59) in Group A but not in Group B (104+/-65 versus 115+/-68); the thallium severity index in Group A was significantly lower than that in Group B, but there was no significant difference in BMIPP abnormality between them. The BMIPP severity index correlated significantly with that of thallium in both groups. However, the regression line in Group A shifted downward and was statistically different compared with that in Group B. Regional function at an acute stage was significantly improved from 107+/-31 to 70+/-31 s.d./chord during follow-up in Group A but not in Group B (109+/-62 versus 106+/-52). The ratio of the thallium severity index to that of BMIPP at an acute stage was significantly related to improved regional wall motion during follow-up in the reperfused patients (y=-53x + 65, r=0.667). CONCLUSION: Preinfarction angina preserves myocyte viability relative to fatty acid metabolism, resulting in augmented perfusion-metabolism mismatch and functional improvement in patients undergoing successful reperfusion, indicating cardioprotective effects of preinfarction angina.

Aged↗